There is considerable evidence that susceptibility to epileptic seizures in women is affected by changes in the ovarian steroids, progesterone and estrogen, that are associated with the various reproductive stages (puberty, menstrual cycles, pregnancy, lactation, menopause) experienced by women throughout their life span. Changes in ovarian steroids also alter other brain functions, such as mood, anxiety, cognition and neural degeneration. However, the mechanism by which progesterone or estrogen alter neuronal function in the brain remain unclear. Thus, studies which examine neuronal-steroidal interactions on brain function can make important contributions to the improvement of women's health. With respect to epilepsy, progress in the study of this disease will be greatly enhanced by the development of a new animal model. This study will use a novel model, the lactating rat, which has been shown to be refractory to epileptic seizure induction mediated by excitatory amino acids acting through NMDA receptors. NMDA receptor-mediated cell activation is thought to underlie seizure activity in humans. The lactating rat does not exhibit NMDA receptor-mediated seizure behavior; it is protected against neuronal damage and cell death that accompany seizure activity; and it has elevated levels of progesterone that contribute to the protection. Therefore, this novel model exhibits unique neuronal-steroidal interactions that alter brain function. The purposed experiments are important because they have the potential to identify neuronal systems that can inhibit NMDA receptor-mediated seizure induction. One such candidate is the GABAergic system which is the major inhibitory system in the brain. Of particular interest is the GABAA receptor that has been shown to interact with neuroactive steroids. The mechanism by which progesterone, or its neurosteroid metabolites, offers protection against seizure induction will provide significant new information that will be relevant to our understanding of steroid hormone effects of brain function. By identifying neuronal and steroidal mechanisms by which epileptic seizure induction can be inhibited, these results will be used to search for similar mechanisms in the primate.